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Glucose-Induced Insulin Hypersecretion in Lipid-Infused Healthy Subjects Is Associated with a Decrease in Plasma Norepinephrine Concentration and Urinary Excretion

Université Paris 7 Centre National de la Recherche Scientifique ESA 7059 (C.M., C.C., L.C., M.V., A.K.), 75251 Paris cedex 05, France; Groupe Hospitalier Necker-Enfants-Malades (INSERM CIC 9303) (N.B., J.-L.B.), Laboratoire de Pharmacologie-Néphrologie (A.G., J.-L.E.), Hôpital Necker, INSERM U 342 (G.V.), Hôpital St Vincent de Paul, 75743 Paris Cedex 15, France; Lipha Merck (P.A., M.K.), 91475 Chilly-Mazarin Chilly-Mazarin, France

Address all correspondence and requests for reprints to: Christophe Magnan, Université Paris 7, Centre National de la Recherche Scientifique ESA 7059, Case 7126, 2 place Jussieu, 75251 Paris cedex 05, France. E-mail: magnan{at}paris7.jussieu.fr

Abstract

We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg^-1) followed by an hyperglycemic clamp (10 mg·kg^-1·min^-1, during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P < 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 ± 0.08 vs. 0.42 ± 0.06 ng/ml, P < 0.05; urinary excretion: 800 ± 70 vs. 620 ± 25 nmol/24 h, P < 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 ± 98 vs. 310 ± 45 pM, P < 0.05; plasma C-peptide 3.5 ± 0.2 vs. 1.7 ± 0.2 nM, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone.

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